Objective To investigate the association between silent mating-type information regulation 2 homolog 3 (SIRT3) gene variation and the risk of non-alcoholic fatty liver disease (NAFLD) and explore the gain-of-function effect of SIRT3 in a mouse model of NAFLD.Methods Blood samples were collected from 374 patients with NAFLD and 372 health control subjects at the Health Examination Center of Southwest Hospital from March 2014 to March 2015.Genome DNA was extracted from the samples for rs11246020 genotyping using Mass-Array system,and the genotype distribution of rs11246020 was analyzed.A plasmid carrying human SIRT3 gene was transfected in a mouse model of NAFLD,and in 8 weeks later,the biochemical indexes and levels of inflammatory cytokines in the serum and liver of the mice were evaluated;the pathology of the liver tissues was observed with HE and oil Red O staining,and the expression levels of Pparα,Acox1,cpt1a,and cpt1b mRNAs and SIRT3 protein in the liver were detected using real-time PCR and Western blotting.Results Compared with the control group,the patients with NAFLD showed a significantly decreased frequency of GA + AA genotype and an increased frequency of GG genotype of rs11246020 in SIRT3 gene (P < 0.05).In the mouse model of NAFLD,over-expression of human SIRT3 in the liver significantly reduced the levels of total cholesterol,triglyceride,and free fatty acids in both the serum and the liver (P < 0.05) and obviously lowered the expression levels of Pparα and Acox1 mRNAs in the liver (P < 0.05).Pathological examination of the liver tissue from the mice with SIRT3 over-expression revealed significantly reduced accumulation of fat vacuoles and lipid droplets.SIRT3 over-expression also effectively controlled the weight gain in the mice (P < 0.05).Conclusion SIRT3 gene variation is associated with the risk of NAFLD,and SIRT3 over-expression improves NALFD in mice possibly by modulating fatty acid metabolism.
目的 应用PCR-DGGE方法研究抗癌剂替吉奥对肠道菌群的影响.方法 取BALB/c小鼠10只,灌服替吉奥(441 mg/kg)7 d.应用PCR-DGGE方法获得肠道菌群分子指纹图谱,进行相似性、多样性分析及优势条带的序列分析.结果 实验0d与实验7d的小鼠肠道菌群结构差异存在统计学意义(P<0.01).结论 替吉奥能够杀灭肠道中的有益菌,促使致病菌过度生长,导致肠道菌群严重失调.